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重症新型冠状病毒肺炎患者的临床生物学特征与克隆性造血

Clinico-Biological Features and Clonal Hematopoiesis in Patients with Severe COVID-19.

作者信息

Duployez Nicolas, Demonchy Jordane, Berthon Céline, Goutay Julien, Caplan Morgan, Moreau Anne-Sophie, Bignon Anne, Marceau-Renaut Alice, Garrigue Delphine, Raczkiewicz Imelda, Geffroy Sandrine, Bucci Maxime, Alidjinou Kazali, Demaret Julie, Labalette Myriam, Brousseau Thierry, Dupont Annabelle, Rauch Antoine, Poissy Julien, Susen Sophie, Preudhomme Claude, Quesnel Bruno

机构信息

UMR 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University Lille, CNRS, Inserm, CHU Lille, F-59000 Lille, France.

Department of Hematology, CHU Lille, F-59000 Lille, France.

出版信息

Cancers (Basel). 2020 Jul 21;12(7):1992. doi: 10.3390/cancers12071992.

Abstract

Advanced age or preexisting comorbidities have been characterized as risk factors for severe coronavirus disease 2019 (COVID-19) cases requiring hospitalization and intensive care. In recent years, clonal hematopoiesis (CH) of indeterminate potential (CHIP) has emerged as a risk factor for chronic inflammatory background and subsequent aging-associated diseases. The purpose of this study was to identify biological factors (particularly leukocyte subtypes and inflammatory markers) associated with a risk of clinical deterioration (i.e., orotracheal intubation (OTI)) and to determine whether CH was likely to influence clinical and biological behavior in patients with severe COVID-19 requiring hospitalization. Here, we describe clinical and biological features, including the screening of CHIP mutants in a well-annotated cohort of 122 hospitalized patients with a laboratory-confirmed diagnosis of COVID-19 (55% requiring OTI). We showed that elevated white blood cell counts, especially neutrophils and high C-reactive protein (CRP) levels at admission, were associated with an increased requirement of OTI. We noticed a high prevalence of CH (25%, 38%, 56%, and 82% of patients aged <60 years, 60-70 years, 70-80 years, and >80 years) compared to a retrospective cohort of patients free of hematological malignancy explored with the same pipelines (10%, 21%, 37%, and 44%). However, the existence of CH did not significantly impact clinical outcome, including OTI or death, and did not correlate with other laboratory findings.

摘要

高龄或既往存在的合并症已被确定为需要住院和重症监护的2019冠状病毒病(COVID-19)重症病例的风险因素。近年来,不明意义的克隆性造血(CHIP)已成为慢性炎症背景及随后与衰老相关疾病的风险因素。本研究的目的是确定与临床恶化风险(即经口气管插管(OTI))相关的生物学因素(特别是白细胞亚型和炎症标志物),并确定CH是否可能影响需要住院的重症COVID-19患者的临床和生物学行为。在此,我们描述了临床和生物学特征,包括在122例经实验室确诊为COVID-19的住院患者(55%需要OTI)的详细队列中筛查CHIP突变体。我们发现,入院时白细胞计数升高,尤其是中性粒细胞计数升高和C反应蛋白(CRP)水平升高,与OTI需求增加相关。我们注意到,与使用相同流程探索的无血液系统恶性肿瘤的回顾性患者队列相比,CH的患病率较高(年龄<60岁、60-70岁、70-80岁和>80岁的患者分别为25%、38%、56%和82%)(分别为10%、21%、37%和44%)。然而,CH的存在并未显著影响临床结局,包括OTI或死亡,也与其他实验室检查结果无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c81/7409316/addd1b716e66/cancers-12-01992-g001.jpg

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